Study Comparing Conventional Dose Combination RVD to High-Dose Treatment With ASCT in the Initial Myeloma up to 65 Years

NCT ID: NCT01191060

Last Updated: 2019-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2018-11-30

Brief Summary

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Objective of this study is to determine if, in the era of novel drugs, high dose therapy (HDT) is still necessary in the initial management of multiple myeloma in younger patients. HDT as compared to conventional dose treatment would be considered superior if it significantly prolongs Progression-free survival (by at least 9 months).

Detailed Description

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Study design Phase III, multicenter, randomized, open-label study designed to evaluate the clinical benefit from the drug combination RVD without immediate high-dose therapy (HDT) followed by lenalidomide maintenance (Arm A) versus RVD plus HDT and PBSCT followed by lenalidomide maintenance (Arm B).

Conditions

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Myeloma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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lenalidomide, bortezomib with ASCT

RVD q 21 days (2 cycles) Collection of peripheral blood stem cells (PBSCs) using cyclophosphamide and GCSF (type Granocyte® or equivalent)

Autologous stem cell transplant:

Melphalan: infused over two days (day -2 and day -1) or as a single infusion (day-2) according to institutional practice Re-infusion of PBSCs RVD q 21 days (2 cycles) Maintenance Lenalidomide q28 days (12 months)

Group Type EXPERIMENTAL

Lenalidomide, Bortezomib

Intervention Type DRUG

Lenalidomide Bortezomib Dexamethasone cycles:

Number of cycles: 5 cycles for arm B

Cycle length

Dosage:

* Lenalidomide: 25 mg/day on days 1-14 of each cycle
* Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle

Maintenance phase (12 months):

Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed

lenalidomide, bortezomib without ASCT

RVD q 21 days (2 cycles) Collection of peripheral blood stem cells (PBSCs) using cyclophosphamide and GCSF (type Granocyte® or equivalent) RVD q 21 days (5 cycles) Maintenance Lenalidomide q28 days (12 months)

Group Type EXPERIMENTAL

Lenalidomide, Bortezomib

Intervention Type DRUG

Lenalidomide/Bortézomib/Dexamethasone cycles:

Number of cycles: 8 cycles for arm A

Cycle length

Dosage:

* Lenalidomide: 25 mg/day on days 1-14 of each cycle
* Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle

Maintenance phase (12 months):

Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed

Interventions

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Lenalidomide, Bortezomib

Lenalidomide/Bortézomib/Dexamethasone cycles:

Number of cycles: 8 cycles for arm A

Cycle length

Dosage:

* Lenalidomide: 25 mg/day on days 1-14 of each cycle
* Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle

Maintenance phase (12 months):

Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed

Intervention Type DRUG

Lenalidomide, Bortezomib

Lenalidomide Bortezomib Dexamethasone cycles:

Number of cycles: 5 cycles for arm B

Cycle length

Dosage:

* Lenalidomide: 25 mg/day on days 1-14 of each cycle
* Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle

Maintenance phase (12 months):

Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed

Intervention Type DRUG

Other Intervention Names

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Lenalidomide (REVLIMID®) Bortezomib (VELCADE®) Lenalidomide (REVLIMID®) Bortézomib (VELCADE®)

Eligibility Criteria

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Inclusion Criteria

(with labs performed within 21 days of initiation of protocol therapy):

* Patients diagnosed with multiple myeloma based on International Myeloma Foundation 2003 Diagnostic Criteria.
* Patients must have symptomatic myeloma with myeloma-related organ damage.
* Patients must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains.
* Age between 18 and 65 years at the time of signing the informed consent document.
* ECOG performance status \<2 (Karnofsky ≥ 60%)
* Negative HIV blood test

Exclusion Criteria

* Participants must not have been treated with any prior systemic therapy for multiple myeloma. Treatment by localized radiotherapy is not an exclusion criterion if an interval of at least two weeks between the end of radiotherapy and initiation of protocol therapy entry in the study is observed. Similarly, the dose of corticosteroids received by the participant should not exceed the equivalent of 160 mg of dexamethasone over a two-week period before initiation of protocol therapy.
* Primary amyloidosis (AL) or myeloma complicated by amylosis.
* Participants may not be receiving any other study investigational agents.
* Participants with known brain metastases
* Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to study agents
* Platelet count \< 50,000/mm3 per µLwithin 21 days of initiation of protocol therapy. Transfusion within 7 days of screening is not allowed to meet platelet eligibility criteria.
* ANC \< 1,000 cells/mm3 within 21 days of initiation of protocol therapy. Growth factor within 7 days of screening is not allowed to meet ANC eligibility criteria.
* Hemoglobin \< 8.0 g/dL within 21 days of initiation of protocol therapy. Transfusion may be used to meet hemoglobin eligibility criteria.
* Hepatic impairment, defined a bilirubin \> 1.5 x institutional upper limit of normal (ULN) \> 2 mg/dL (Patients with benign hyperbilirubinemia (e.g., Gilbert's syndrome) are eligible) and or AST (SGOT), or ALT (SGPT), or alkaline phosphatase \> 2 x ULN
* Renal insufficiency, defined as serum creatinine \> 2.5 mg/dl and/or creatinine clearance \< \<40 60 ml/min (actual or calculated). The Cockgroft-Gault formula should be used for calculating creatinine clearance values, and may be located in Section 4.2
* Respiratory compromise, defined as ventilation tests and with DLCO \< 50%
* Participant must not demonstrate with clinical signs of heart or coronary failure, or evidence of LVEF \< 40%. Participant must not have with myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA Appendix VII) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
* Intercurrent illness including, but not limited to ongoing or active severe infection, known (active or not) infection with hepatitis B or C virus, poorly controlled diabetes, severe uncontrolled psychiatric disorder or psychiatric illness/social situations that would limit compliance with study requirements.
* Participant with previous history of another malignant condition, except for basal cell carcinoma and stage I cervical cancer
* Female participant who is pregnant or breast-feeding
* Inability to comply with an anti-thrombotic treatment regimen
* Peripheral neuropathy ≥ Grade 2 peripheral neuropathy on clinical examination within 21 days of initiation of protocol therapy
* Mental illness likely to interfere with participation in the study and Adults under juridical protection
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dana-Farber Cancer Institute

OTHER

Sponsor Role collaborator

Celgene Corporation

INDUSTRY

Sponsor Role collaborator

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role collaborator

University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MICHEL ATTAL, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Toulouse

Locations

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CH du Pays D'Aix

Aix-en-Provence, , France

Site Status

CHRU - Hôpital Sud Amiens

Amiens, , France

Site Status

CHU d'Angers

Angers, , France

Site Status

Centre Hospitalier Argenteuil Victor Dupouy

Argenteuil, , France

Site Status

Centre Hospitalier H.Duffaut

Avignon, , France

Site Status

Centre Hospitalier de la côte basque

Bayonne, , France

Site Status

Hôpital Jean Minjoz

Besançon, , France

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Centre Hospitalier de Blois

Blois, , France

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Hôpital Avicenne

Bobigny, , France

Site Status

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, , France

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Hôpital A.Morvan

Brest, , France

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CHU Caen Côte de Nacre

Caen, , France

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Centre François Baclesse

Caen, , France

Site Status

CH René Dubos

Cergy-Pontoise, , France

Site Status

Centre Hospitalier William Morey

Chalon-sur-Saône, , France

Site Status

CH Chambéry

Chambéry, , France

Site Status

Hôpital Antoine Béclère

Clamart, , France

Site Status

Hôpital d'instruction des armées Percy

Clamart, , France

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CHU d'Estaing

Clermont-Ferrand, , France

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Pole Santé République

Clermont-Ferrand, , France

Site Status

CH Louis Pasteur - Colmar

Colmar, , France

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CH Sud Francilien

Corbeil-Essonnes, , France

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CHU Henri Mondor

Créteil, , France

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CHRU Dijon

Dijon, , France

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Centre Hospitalier Général - Dunkerque

Dunkirk, , France

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Hôpital A.Michallon

Grenoble, , France

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Centre hospitalier départemental - La Roche sur Yon cedex

La Roche-sur-Yon, , France

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CH de Chartres - Hôpital Louis Pasteur

Le Coudray, , France

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Centre Jean Bernard

Le Mans, , France

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Centre hospitalier Le Mans

Le Mans, , France

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CHRU - Hôpital Claude Huriez

Lille, , France

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CHU de Limoges

Limoges, , France

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Centre hospitalier Bodelio

Lorient, , France

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CHU - Hôpital Edouard Herriot

Lyon, , France

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Centre Léon Bérard

Lyon, , France

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Institut Paoli Calmettes

Marseille, , France

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CH Meaux

Meaux, , France

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Hopital E Muller

Mulhouse, , France

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Hôpitaux de Brabois

Nancy, , France

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Centre Catherine de Sienne

Nantes, , France

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CHRU - Hôtel Dieu

Nantes, , France

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Hôpital Archet 1

Nice, , France

Site Status

Hôpital de l'Archet

Nice, , France

Site Status

Groupe Hospitalo-Universitaire Carémeau

Nîmes Cédex 9, , France

Site Status

Institut Curie

Paris, , France

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Hôpital Cochin

Paris, , France

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Hôpital Saint-Louis

Paris, , France

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Hôpital St-Antoine

Paris, , France

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CH Saint Jean

Perpignan, , France

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CHRU - Hôpital du Haut Lévêque

Pessac, , France

Site Status

Centre Hospitalier Lyon sud

Pierre-Bénite, , France

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CHRU - Hôpital Jean Bernard

Poitiers, , France

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Centre Hospitalier de la région d'Annecy

Pringy, , France

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Hôpital R.Debré

Reims, , France

Site Status

CHRU - Hôpital de Pontchaillou

Rennes, , France

Site Status

CHRU - Hôpital Sud

Rennes, , France

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Centre Henri Becquerel

Rouen, , France

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Centre Hospitalier Yves le Foll

Saint-Brieuc, , France

Site Status

Centre René Huguenin

Saint-Cloud, , France

Site Status

Centre Hospitalier Départemental - La réunion St Denis

Saint-Denis, , France

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Groupe Hospitalier Sud Réunion

Saint-Pierre, , France

Site Status

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, , France

Site Status

Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

Site Status

University Hospital of Toulouse, Purpan

Toulouse, , France

Site Status

CHRU - Hôpital Bretonneau

Tours, , France

Site Status

Centre Hospitalier de Valence

Valence, , France

Site Status

CH Bretagne Atlantique Vannes et Auray

Vannes, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Countries

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France

References

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Rosinol L, Hebraud B, Oriol A, Colin AL, Rios Tamayo R, Hulin C, Blanchard MJ, Caillot D, Sureda A, Hernandez MT, Arnulf B, Mateos MV, Macro M, San-Miguel J, Belhadj K, Lahuerta JJ, Garelik MB, Blade J, Moreau P. Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma. Front Oncol. 2023 Nov 2;13:1197340. doi: 10.3389/fonc.2023.1197340. eCollection 2023.

Reference Type DERIVED
PMID: 38023148 (View on PubMed)

Noori S, Wijnands C, Langerhorst P, Bonifay V, Stingl C, Touzeau C, Corre J, Perrot A, Moreau P, Caillon H, Luider TM, Dejoie T, Jacobs JFM, van Duijn MM. Dynamic monitoring of myeloma minimal residual disease with targeted mass spectrometry. Blood Cancer J. 2023 Feb 24;13(1):30. doi: 10.1038/s41408-023-00803-z. No abstract available.

Reference Type DERIVED
PMID: 36828828 (View on PubMed)

Langerhorst P, Noori S, Zajec M, De Rijke YB, Gloerich J, van Gool AJ, Caillon H, Joosten I, Luider TM, Corre J, VanDuijn MM, Dejoie T, Jacobs JFM. Multiple Myeloma Minimal Residual Disease Detection: Targeted Mass Spectrometry in Blood vs Next-Generation Sequencing in Bone Marrow. Clin Chem. 2021 Nov 26;67(12):1689-1698. doi: 10.1093/clinchem/hvab187.

Reference Type DERIVED
PMID: 34643690 (View on PubMed)

Samur MK, Aktas Samur A, Fulciniti M, Szalat R, Han T, Shammas M, Richardson P, Magrangeas F, Minvielle S, Corre J, Moreau P, Thakurta A, Anderson KC, Parmigiani G, Avet-Loiseau H, Munshi NC. Genome-Wide Somatic Alterations in Multiple Myeloma Reveal a Superior Outcome Group. J Clin Oncol. 2020 Sep 20;38(27):3107-3118. doi: 10.1200/JCO.20.00461. Epub 2020 Jul 20.

Reference Type DERIVED
PMID: 32687451 (View on PubMed)

Roussel M, Hebraud B, Hulin C, Perrot A, Caillot D, Stoppa AM, Macro M, Escoffre M, Arnulf B, Belhadj K, Karlin L, Garderet L, Facon T, Guo S, Weng J, Dhanasiri S, Leleu X, Moreau P, Attal M. Health-related quality of life results from the IFM 2009 trial: treatment with lenalidomide, bortezomib, and dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma. Leuk Lymphoma. 2020 Jun;61(6):1323-1333. doi: 10.1080/10428194.2020.1719091. Epub 2020 Feb 22.

Reference Type DERIVED
PMID: 32090636 (View on PubMed)

Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. doi: 10.1056/NEJMoa1611750.

Reference Type DERIVED
PMID: 28379796 (View on PubMed)

Dunavin NC, Wei L, Elder P, Phillips GS, Benson DM Jr, Hofmeister CC, Penza S, Greenfield C, Rose KS, Rieser G, Merritt L, Ketcham J, Heerema N, Byrd JC, Devine SM, Efebera YA. Early versus delayed autologous stem cell transplant in patients receiving novel therapies for multiple myeloma. Leuk Lymphoma. 2013 Aug;54(8):1658-64. doi: 10.3109/10428194.2012.751528. Epub 2012 Dec 31.

Reference Type DERIVED
PMID: 23194056 (View on PubMed)

Other Identifiers

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09 110 01

Identifier Type: -

Identifier Source: org_study_id

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